Autoimmune diseases occur when the body’s immune system mistakenly attacks its own healthy tissues, viewing them as foreign invaders. This internal conflict triggers a systemic inflammatory response intended to neutralize the perceived threat. Fever is a common consequence of this misdirected immune activity. The resulting elevation in body temperature is a physical manifestation of this underlying inflammatory process.
Understanding How Autoimmunity Causes Fever
Fever in the context of autoimmunity is generally not a response to an external infection, but rather a direct result of uncontrolled internal inflammation. This process is driven by the release of powerful signaling proteins known as inflammatory mediators, or cytokines. Pro-inflammatory cytokines, especially interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-\(\alpha\)), act as endogenous pyrogens, meaning they are heat-inducing substances produced within the body. These cytokine signals travel through the bloodstream and eventually reach the hypothalamus in the brain, which functions as the body’s thermostat.
The cytokines instruct the hypothalamus to raise the body’s temperature set point. This new, higher set point triggers physiological responses like shivering and peripheral vasoconstriction to conserve heat and raise the body temperature. The hypothalamic temperature shift is achieved through the local synthesis of prostaglandins, particularly prostaglandin E2 (PGE2). The continuous release of these inflammatory cytokines maintains the elevated set point, leading to persistent or recurrent fevers.
Primary Autoimmune Conditions Where Fever is a Main Symptom
Systemic Lupus Erythematosus (SLE) is a well-recognized autoimmune disease where fever is a frequent symptom, often signaling an increase in disease activity. Fever occurs in a large percentage of SLE patients, sometimes presenting as a low-grade temperature that remains below 101°F. It is usually considered a feature of active lupus only after potential infections have been thoroughly ruled out.
Another condition defined by its characteristic fever pattern is Adult-Onset Still’s Disease (AOSD), a rare type of inflammatory arthritis that affects the entire body. The fever in AOSD is typically high and spiking, often reaching over 102°F once or twice a day, a pattern referred to as quotidian. The temperature often returns to normal or near-normal levels between these spikes, and the fever is frequently accompanied by a transient, salmon-colored skin rash and joint pain.
Vasculitis syndromes, which involve the inflammation of blood vessel walls, also frequently cause systemic fevers. Polyarteritis Nodosa (PAN), a necrotizing vasculitis affecting medium-sized arteries, often presents with non-specific systemic symptoms, including fever, malaise, and unintended weight loss. Giant Cell Arteritis (GCA), which primarily affects large arteries in the head and neck and is more common in adults over 50, may also present with persistent fever. In some instances, GCA can present as a fever of unknown origin, making diagnosis particularly challenging.
Differentiating Auto-inflammatory Syndromes
While autoimmune diseases are a major cause of non-infectious fever, it is important to distinguish them from auto-inflammatory syndromes, which are also characterized by recurrent, unprovoked fevers. The fundamental difference lies in the specific branch of the immune system involved in the malfunction. Autoimmune diseases arise from a problem in the adaptive immune system, which uses highly specific components like T-cells and B-cells to generate targeted antibodies against the body’s own tissues.
Auto-inflammatory syndromes, in contrast, result from a dysfunction of the innate immune system, which is the body’s first line of non-specific defense. This innate system becomes hyperactive, leading to uncontrolled, spontaneous inflammation without the presence of autoantibodies or self-reactive T-cells. These conditions are often monogenic, meaning they are caused by a single gene mutation, and manifest as periodic fever syndromes.
Familial Mediterranean Fever (FMF) is a well-known example of an auto-inflammatory syndrome, causing recurrent, self-limiting episodes of fever, often accompanied by abdominal pain, chest pain, or joint pain. The key feature is the episodic nature of the inflammation, which is unprovoked by external factors and resolves spontaneously. The presence of recurrent fevers without the typical markers of adaptive immunity involvement helps physicians differentiate these from classic autoimmune diseases.
The Diagnostic Steps for Unexplained Fevers
When a persistent fever has no clear infectious source, it is often investigated as a Fever of Unknown Origin (FUO), a process that involves a systematic exclusion of common causes. The initial diagnostic approach centers on ruling out the most frequent causes, which include infections and malignancy. This requires a comprehensive history, physical examination, and basic laboratory work.
If the initial workup is inconclusive, physicians, often in consultation with a rheumatologist, will screen for systemic inflammatory conditions, including autoimmune diseases. Laboratory tests measure generalized markers of inflammation, such as the Erythrocyte Sedimentation Rate (ESR) and C-Reactive Protein (CRP), which are typically highly elevated in autoimmune fevers. Specific antibody tests, such as the Antinuclear Antibody (ANA) test, are also used to detect the presence of the self-targeting antibodies characteristic of many autoimmune conditions like SLE.
Further investigation may involve imaging studies or specific biopsies, such as a temporal artery biopsy for suspected Giant Cell Arteritis, to confirm a diagnosis. The pattern and characteristics of the fever itself, such as the quotidian spiking of AOSD, provide important diagnostic clues. A diagnosis of autoimmune fever is often one of exclusion, made when a persistent, inflammatory fever cannot be attributed to any infectious or cancerous cause.